Background: Chronic inflammation is related to both obesity and diabetes. Our aim was to investigate to what extent this inflammation contributes to the association between obesity and diabetes. Methods. Using a case-cohort design, we followed 567 middle-aged individuals who developed diabetes and 554 who did not over 9 years within the ARIC Study. Weighted Cox proportional hazards analyses permitted statistical inference to the entire cohort. Results: Obese individuals (BMI≥30 kg/m§ssup§2§esup§), compared to those with BMI<25 kg/m§ssup§2§esup§, presented a large increased risk of developing diabetes (HR[obesity]=6.4, 95%CI 4.5-9.2), as did those in the highest (compared to the lowest) quartile of waist circumference (HR[waist]=8.3, 95%CI 5.6-12.3), in analyses adjusted for age, gender, ethnicity, study center, and parental history of diabetes. Notably, further adjustment for adiponectin and inflammation markers halved the magnitude of these associations (HR[obesity]=3.2, 95%CI 2.1-4.7; and HR[waist]=4.2, 95%CI 2.8-6.5). In similar modeling, attenuation obtained by adding fasting insulin, instead of these markers, was only slightly more pronounced HR[obesity]=2.7, 95%CI 1.7-4.1; and HR[waist]=3.6, 95%CI 2.3-5.8). Conclusions: The marked decrease in the obesity-diabetes association after taking into account inflammation markers and adipokines indicates their major role in the pathways leading to adult onset of diabetes in obese individuals.
Bibliographical noteFunding Information:
The authors thank the staff and participants of the ARIC study for their important contributions. The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C. Measurement of inflammatory markers and adiponectin was supported in an ancillary study by National Institute of Diabetes, Digestive and Kidney Diseases Grant R01-DK056918. B. B. Duncan, M. I. Schmidt, and V. C. Luft received support from a Centers of Excellence Grant from the CNPq (Brazilian National Council for Scientific and Technological Development).
- Epidemiologic studies